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Redistribution of adhering junctions in human endometrial epithelial cells during the implantation window of the menstrual cycle

Abstract

The human uterine epithelium is characterised by remarkable plasticity with cyclic changes in differentiation that are controlled by ovarian steroid hormones to optimise conditions for embryo implantation. To understand whether and how cell–cell adhesion is affected, the localisation of junction proteins was studied throughout the menstrual cycle. Expression patterns were examined by immunofluorescence in 36 human endometrial specimens of different cycle stages. Antibodies against the desmosomal proteins desmoplakin 1/2 (Dp 1/2) and desmoglein 2 (Dsg 2), the adherens junction proteins E-cadherin and β-catenin and also the common junctional linker protein plakoglobin showed a strong subapical staining during the proliferative phase until the early luteal phase (day 20). In the mid- to late luteal phase, however, these junctional proteins redistributed over the entire lateral plasma membranes. In contrast, tight junction proteins (ZO-1, claudin 4) remained at their characteristic subapical position throughout the menstrual cycle. mRNA levels of Dp 1/2, E-cadherin and ZO-1 obtained by real time RT-PCR were not significantly changed during the menstrual cycle. The observed redistribution of desmosomes and adherens junctions coincides with the onset of the so called implantation window of human endometrium. We propose that this change is controlled by ovarian steroids and prepares the endometrium for successful trophoblast invasion.

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Acknowledgments

Thanks are due to Dr. C. Krusche for useful comments and help with primer design and PCR protocol and to Diana Seelis-Schmidt, Claudia Schmitz and Vanessa Creutz for excellent technical assistance.

Author information

Correspondence to Irmgard Classen-Linke.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (MPG 6180 kb). Online Resource 1: 3-D reconstruction of a 9 µm thick cryosection through endometrial glands from the functionalis layer of the endometrium. Staining against Dp 1/2 is concentrated in the subapical region of lateral plasma membranes at day 9 (left). At day 23 the desmosomes are evenly distributed along the whole lateral plasma membrane as visualised by the punctuate staining against Dp 1/2(right). Staining at the apical or the basal membranes was not observed. Reconstructions of 27 consecutive focal plains scanned by confocal LSM. (MPG 6180 kb)

Supplementary material 1 (MPG 6180 kb). Online Resource 1: 3-D reconstruction of a 9 µm thick cryosection through endometrial glands from the functionalis layer of the endometrium. Staining against Dp 1/2 is concentrated in the subapical region of lateral plasma membranes at day 9 (left). At day 23 the desmosomes are evenly distributed along the whole lateral plasma membrane as visualised by the punctuate staining against Dp 1/2(right). Staining at the apical or the basal membranes was not observed. Reconstructions of 27 consecutive focal plains scanned by confocal LSM. (MPG 6180 kb)

Supplementary material 2 (PDF 5304 kb). Online Resource 2: Immunostaining of claudin 4 on glandular endometrial epithelial cells in the proliferative phase (a/day 9) and in the luteal phase (c/day 24) of the menstrual cycle. Merged pictures on the right combined with DAPI staining (b, d). The claudin 4 antibody showed a similar staining as the ZO-1 antibody. Confocal LSM images. Scale bars: 10 µm (PDF 5304 kb)

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Buck, V.U., Windoffer, R., Leube, R.E. et al. Redistribution of adhering junctions in human endometrial epithelial cells during the implantation window of the menstrual cycle. Histochem Cell Biol 137, 777–790 (2012) doi:10.1007/s00418-012-0929-0

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Keywords

  • Desmosome
  • Adherens junction
  • Tight junction
  • Human endometrium
  • Menstrual cycle
  • Implantation